6 ECTS credits
150 h study time

Offer 1 with catalog number 4017584ENR for all students in the 1st semester at a (E) Master - advanced level.

Semester
1st semester
Enrollment based on exam contract
Impossible
Grading method
Grading (scale from 0 to 20)
Can retake in second session
Yes
Enrollment Requirements
Following courses are mutually exclusive: "High Throughput Techniques (6ECTS)" and "High Throughput Techniques (4ECTS)".
Taught in
Faculty
Faculty of Sciences and Bioengineering Sciences
Department
Bio-Engineering Sciences
Educational team
Jo Van Ginderachter
Nick Devoogdt
Steven Ballet (course titular)
Activities and contact hours
39 contact hours Lecture
Course Content

Part Combinatorial Chemistry

The next topics are discussed:

  • Solution Phase Combinatorial Synthesis: Parallel synthesis, One-pot synthesis, scavengers, quenchers, resin-bound reagents, solution phase combinatorial chemistry using dendrimers, classical purification by extraction, fluorous phase chemistry,
  • Solid Phase Combinatorial Synthesis: Resins, linkers, solution phase synthesis versus solid phase synthesis.
  • Mixed versus parallel synthesis,
  • Identification of the active component (Mix-and-split synthesis, micro analysis, Off-bead mass spectrometry, On-bead mass spectrometry, On-bead analysis with NMR spectroscopy, infrared spectrometry, iterative deconvolution, recursive method, positional scanning), encoding of libraries (chemical tagging, binary encoding, radio frequency (RF) markers, laser (optical) encoding, fluorescence encoding),
  • Dynamic combinatorial chemistry
  • Varying case studies

Part of Combinatorial BIO-chemistry:


In this part we review:

  • the construction and screening of genomic and cDNA banks.
  • the selection of peptide libraries via phage-display, introducing M13 gene3 containing phasmids, selection procedures and providing solutions to remediate the reduced performance of virions.
  • the alternative non-phage display systems and screenings, including in vitro selection systems such as SELEX, ribosome display, RNA peptide fusion and compartimentalised systems.
  • the selection techniques for functional entities and in vitro transcription/translation and protein interactions on µ-arrays and the generation of new man-made proteins.
  • Techniques to determine cellular characteristics via fluorescence (immunohistochemistry, fluorescence microscopy, flow cytometry)
  • Mass cytometry of cells
  • Techniques to determine the epigenome of cells (ATAC-seq, ChIP-seq)
  • Techniques to determine the transcriptome of individual cells (single cell RNA-seq)

 

Part Drug Design:

The next topics are presented:

  • Introduction: An overview of the different stages in drug development is given. Additionally, a historical background (febrifugine, efedrine) and the different sources for discovery of biologically active substances are presented
  • Lead discovery, hit-to-lead process, lead optimization
  • (Quantitative) Structure Activity Relationships (Q)SAR, Hansch analysis, Topliss analysis, Craig plot
  • Concept of Molecular modelling techniques
  • Case study: Captopril: rational design of an ACE-inhibitor (enzyme inhibitor)
  • Case study: Losartan: efficient synthesis of an Angiotensine II antagonist
  • Case study: Cimetidine: rational design of an H2-antagonist, Synthesis of famotidine and ranitidine
  • Case study: Rational development of designed multiple ligands


 

Course material
Digital course material (Required) : Part Combinatorial Chemistry, Lecture notes, powerpoint presentations and course text
Digital course material (Required) : Part of Combinatorial BIO-chemistry, Lecture notes and powerpoint presentations
Digital course material (Required) : Part Drug Design, Lecture notes and powerpoint presentations
Handbook (Recommended) : An introduction to Medicinal Chemistry, Graham L. Patrick, 5th edition, Oxford press, 9780198749691, 2017
Additional info

N/A

Learning Outcomes

General competences

Part Combinatorial Chemistry


The student

  • understands the principles of combinatorial chemistry, both in solution and on solid phase.
  • understands the reactivity of the different conversions used during this course
  • is acquainted with techniques (synthetic and analytical) used in combinatorial chemistry and knows their advantages and disadvantages.

Part of Combinatorial BIO-chemistry


The student understands

  • the various techniques used to construct immense large combinatorial libraries of bio-molecules
  • their screening in a high-throughput approach for functional biochemical molecules
  • the techniques to determine characteristics of individual cells, at the level of proteins, epigenome and transcriptome

 

Part Drug Design


The student is acquainted with 

  • the different stages in clinical development
  • formulating structure-activity relationships
  • the biochemical mode of action of the discussed drugs 
  • the important physicochemical properties of drugs (and clinical candidates)
  • the synthesis (and strategy) of the discussed drugs
  • providing the theoretical and practical aspects of drug design
  • demonstrating how the physicochemical background of molecular interactions is used for drug design.

Grading

The final grade is composed based on the following categories:
Oral Exam determines 67% of the final mark.
Written Exam determines 33% of the final mark.

Within the Oral Exam category, the following assignments need to be completed:

  • Combinatorial Chemistry with a relative weight of 1 which comprises 16.8% of the final mark.

    Note: Oral examination with written preparation.
  • Combinatorial BIO-chemistry with a relative weight of 2 which comprises 33.5% of the final mark.

    Note: Oral examination with written preparation.

    The final marks are the average of the two parts,traking into account the number of hours foreseen for each subpart.
  • Drug Design with a relative weight of 1 which comprises 16.8% of the final mark.

    Note: Oral examination with written preparation.

Within the Written Exam category, the following assignments need to be completed:

  • Combinatorial Chemistry with a relative weight of 1 which comprises 16.5% of the final mark.

    Note: Written examination
  • Drug Design with a relative weight of 1 which comprises 16.5% of the final mark.

    Note: Written examination

Additional info regarding evaluation

Part Combinatorial Chemistry (Prof S. Ballet)
Oral exam with written preparation and written exam

Part of Combinatorial BIO-chemistry (Prof Van Ginderachter/Devoogdt)
Oral examination with written preparation.

Part Drug Design (Prof S. Ballet)

Oral exam with written preparation and written exam

The final marks are calculated as the average of the three parts. The student must obtain a minimum grade of 10/20 for each part in order to succeed for the complete course.

If the student obtains at least half of the score for an individual part, partial marks are transferred to the second session and to the next academic year. Students may not relinquish partial marks.

Allowed unsatisfactory mark
The supplementary Teaching and Examination Regulations of your faculty stipulate whether an allowed unsatisfactory mark for this programme unit is permitted.

Academic context

This offer is part of the following study plans:
Master of Bioengineering Sciences: Chemistry and Bioprocess Technology: Biochemical Biotechnology (only offered in Dutch)